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Differential Diagnosis

Different causes of the bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings.

These features have discussed in the below table:

Category	Sub-category	Diseases		History	Clinical manifestation						Laboratory testing					Comments
					Mucosal bleeding	Petechia	Ecchymoses	Menorrhagia	Hematoma	Hemarthrosis	Platelet count	Bleeding time (BT)	Prothrombin time (PT)	Activated partial thromboplastin time (aPTT)	Thrombin time (TT)
Platelet disorders	Thrombocytopenia	Infection-Induced thrombocytopenia		History of prior infection	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	−
		Medications-Induced thrombocytopenia		History of medications such as: Furosemide Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Quinidine Quinine Ranitidine Sulfonamides Linezolid	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	Most important part of treatment is discontinuing of the medication.
		Heparin-Induced thrombocytopenia		Thrombosis Unexplained thrombocytopenia up to 3 weeks after the end of heparin therapy	+	+	+	+	+	+	↓	↑	Normal	Normal	↑	For more information click here: Heparin-induced thrombocytopenia.
		Immune Thrombocytopenic Purpura (ITP)		History of prior infection or no history	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	−
		Inherited Thrombocytopenia		Positive family history	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	−
		Thrombotic Thrombocytopenic Purpura (TTP)		History of: Cancer Bone marrow transplantation Pregnancy Medication Platelet aggregation inhibitors (ticlopidine and clopidogrel) Immunosuppressants (cyclosporine, mitomycin, tacrolimus/FK506, interferon-α) HIV-1 infection	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	−
		Hemolytic Uremic Syndrome		History of: Infections Malignancy, chemotherapy, and ionizing radiation Calcineurin inhibitors and transplantation Pregnancy, HELLP syndrome, and oral contraceptive pill Systemic lupus erythematosis Antiphospholipid antibody syndrome Glomerulopathy	+	+	+	+	+	+	↓	↑	Normal	Normal	Normal	−
	Thromobcytosis	Iron deficiency anemia Inflammatory diseases Splenectomy Essential thrombocytosis		Digital pain Gangrene Erythromelalgia Headache Paresthesias Transient ischemic attacks	−	−	−	−	±	±	↑	Normal or ↑	Normal	Normal	Normal	−
	Qualitative Disorders of Platelet Function	Inherited Disorders of Platelet Function	Glanzmann’s thrombasthenia	Positive family history	+	+	+	+	−	Rare	Normal or ↓	↑	Normal	Normal	Normal	AR inheritance Absence of the platelet Gp IIb/IIIa receptor Diminished for GP 2B-3A on flow cytometry
			Bernard-Soulier syndrome	Positive family history	+	+	+	+	−	−	Normal or ↓	↑	Normal	Normal	Normal	AR inheritance Absence of the platelet Gp Ib-IX-V receptor On PBS: giant platelets Ristocetin - no aggregation
			Wiskott-Aldrich syndrome	Positive family history	+	+	+	+	−	−	Normal or ↓	↑	Normal	Normal	Normal	Anti-WASP antibody can be used to detect presence or absence of WAS protein In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.
			Platelet storage pool disorder (SPD): Hermansky-Pudlak syndrome Chediak-Higashi syndrome Gray platelet syndrome	Positive family history Hairy cell leukemia Cardiovascular bypass	+	+	+	+	−	−	Normal or ↓	↑	Normal	Normal	Normal	AD inheritance Abnormalities of platelet granule formation
		Acquired Disorders of Platelet Function		Uremia Cardiopulmonary bypass Hematologic disorders such as: myeloproliferative and myelodysplastic syndromes	+	+	+	+	±	±	Normal or ↓	↑	Normal	Normal	Normal	−
		Von Willebrand Disease		Easy bruising Epistaxis Oral cavity bleeding Bleeding after dental extraction/surgery Menorrhagia Postpartum hemorrhage	+	+	+	+	±	±	↑	Normal	↑	↑	Normal	See the table below for the details about different types.
Vessel wall disorders	Metabolic and Inflammatory Disorders	Acute febrile illnesses Mixed cryoglobulinemia Monoclonal gammopathies Certain pathogens, such as the rickettsiae causing Rocky Mountain spotted fever Vitamin C deficiency Cushing’s syndrome Chronic glucocorticoid therapy Aging Vasculitis such as Henoch-Schönlein,		History of the underlying disease.	−	+	+	±	−	−	Normal	↑/Normal	Normal	Normal	Normal	−
	Inherited Disorders of the Vessel Wall	Marfan’s syndrome Ehlers-Danlos syndrome Pseudoxanthoma elasticum Hereditary hemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu disease)		Positive family history	−	+	+	±	−	−	Normal	↑/Normal	Normal	Normal	Normal	−
Coagulation factor disorders	Fibrinogen deficiency	Different types of the fibrinogen disorders: Congenital afibrinogenemia Congenital hypofibrinogenemia Fibrinogen storage disease Congenital dysfibrinogenemia Hereditary fibrinogen Aα-Chain amyloidosis Acquired dysfibrinogenemia Congenital hypodysfibrinogenemiaCryofibrinogenemia Acquired hypofibrinogenemia		Epistaxis Easy bruising Menorrhagia Muscle bleeds Hemarthrosis Bleeding from the umbilical cord stump after birth Bleeding after dental surgery or tooth extraction Abnormal bleeding during or after injury, surgery, or childbirth Gastrointestinal hemorrhage Cerebral hemorrhage Thrombosis	−	−	+	+	±	+	Normal	↑	↑	↑	↑	Impaired fibrin cross linking or clot dissolution. The severity of bleeding in patients with fibrinogen disorders can be mild or severe, with higher bleeding risk in those with afibrinogenemia or lower levels of functional fibrinogen. The age of onset is also variable, with earlier onset in those with more severe deficiency.
	Prothrombin deficiency			Easy bruising Epistaxis Soft-tissue hemorrhage Excessive postoperative bleeding Menorrhagia Muscle hematomas Hemarthrosis Intracranial bleeding	−	+	+	+	+	+	Normal	Normal	↑	↑	↑	−
	Factor V deficiency			Excessive bruising with minor injuries Epistaxis Hemarthrosis Menorrhagia Intracerebral hemorrhages Pulmonary hemorrhage	−	_	+	+	+	+	Normal	↑	↑	↑	Normal	The severity of bleeding is only partly related to the degree of factor V deficiency. Some patients with undetectable plasma levels of factor V experience only relatively mild bleeding.
	Factor VII deficiency			Easy bruising Mucosal bleeding Postoperative bleeding Menorrhagia Soft tissue hematomas Thrombosis				+	+	+	Normal		↑	Normal	Normal	Thrombosis occurs in inherited factor VII deficiency most cases are associated with the administration of factor VII replacement therapy
	Factor X deficiency			Prolonged bleeding following circumcision Easy bruising Hematuria Menorrhagia Abortion Postpartum hemorrhage Epistaxis Pseudotumors Intracranial bleeding Hemarthroses		+	+	+	+	+	Normal	Normal	↑	↑	Normal	−
	Factor XII deficiency			Majority,asymptomatic Recurrent miscarriages Painful leg ulcers		_	_	_	_	_	Normal	Normal	Normal	↑	Normal
	High molecular weight kininogen (HMWK) deficiency			Possibility of positive family history of bleeding		_	_	_	_	_	Normal	Normal	Normal	↑	Normal
	Prekallikrein deficiency			Possibility of positive family history of bleeding		_	_	_	_	_	Normal	Normal	Normal	↑	Normal
	Factor XIII deficiency	Types: Sub unit A mutation disease (more common) Sub unit B mutation disease		Possibility of positive family history of bleeding	±	±	±	±	±	±	Normal	Normal	Normal/↑	Normal	Normal	Impaired fibrin cross linking or clot dissolution The severity of factor XIII deficiency bleeds can be different in different patients
	Hemophilia	Type A deficiency		Eeasy bruising Inadequate clotting in trauma or mild injury Spontaneous hemorrhage Hemarthrosis Epistaxis Gingival bleeding	−	−	−	+	+	+	Normal	Normal	Normal	↑	Normal	−
		Type B deficiency		Neonatal bleeding Trauma-related soft-tissue hemorrhage Hemarthrosis Hematomas	−	−	−	+	+	+	Normal	Normal	Normal	↑	Normal	−
		Type C deficiency		Family history Bleeding after surgery or injury	−	−	−	+	Rare	Rare	Normal	Normal	Normal	↑	Normal	−
Rare diseases	Disseminated Intravascular Coagulation			Trauma Burn Crush injury Sepsis Malignancy Obstetric complication: abruption, amniotic fluid embolism Hemolytic anemia	+	+	+	+	+	+	↓	↑	↑	↑	Normal	−
	Vitamin K Deficiency			Bleeding after trauma Epistaxis Hematoma Gastrointestinal bleeding Menorrhagia Hematuria Gum bleeding Oozing from venipuncture sites Easy bruisability	+	−	+	+	+	+	Normal	↑	↑	Normal or mildly prolonged	Normal	−

Different types of Von-Willebrand diseases can be differentiated from each other based on the following table:

Type of VWD		Type of factor deficiency	Prevalence	Inheritance pattern	Clinical manifestations	VWF activity	RIPA	Factor VIII
Type 1		Quantitative/ partial	60-70%	AD	Bleeding severity mild to severe	↓	↓	↓
Type 2	2A	Qualitative	10%	AD/AR	Moderate to severe bleeding	↓	↓	N or ↓
	2B	Qualitative	5%	AD	Thrombocytopenia Moderate to severe bleeding	↓	↑	N or ↓
	2M	Qualitative	<1%	AD/AR	Moderate to severe bleeding	↓	↓	N or ↓
	2N	Qualitative	<1%	AR	Clinically similar to hemophilia A with joint, soft tissue, urinary bleeding	N	N	↓
Type 3		Complete deficiency	1-2%	AR	Clinically similar to hemophilia A with joint and soft tissue bleeding Severe mucosal bleeding	Absent	↓	Low, 1-10%

For more information on Von Willebrand disease, click here.